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Although vitamin B12 deficiency is a well-established cause of severe anaemia with macrocytosis in infants, severe thrombocytopenia has been less commonly reported. In this report, we describe an uncommon case of an infant with severe vitamin B12 deficiency presenting with severe anemia and thrombocytopenia, and discuss its implications as a potentially preventable public health problem.

Case report

An exclusively breastfed eight-month-old girl, who had been unsuccessful with attempts to wean on to solids, presented to the emergency room unwell with fever. She was diagnosed with a right lower lobe pneumonia. Incidentally, she was remarkably pale with mucosal bleeding and fine petechiae on her trunk and limbs. Further history revealed black tarry stools typical of melaena.

On examination, the infant was found to be generally irritable with central hypotonia and significant gross, fine motor delay. At rest, the infant was floppy with frog-leg posturing. She was unable to pull to sit and showed marked head lag, poor head control. She was also unable to track objects of interest or bring her arms to midline and reach for objects. She was also found not to mimic facial expressions or have a social smile.

Laboratory investigations show a severe macrocytic anaemia, thrombocytopenia along with profoundly low B12 levels (Table 1). Although folate and iron studies were within normal range, she was also found to have vitamin D deficiency with hypocalcemia.

Table 1: Laboratory investigations.

The blood film showed marked red cell anisopoikilocytosis with tear drop poikilocytes, stippled cells, macrocytes, many fragmented cells and occasional dysplastic nucleated red cells (Figure 1). Platelet count was low but morphologically normal. White blood cells showed occasional hypersegmented neutrophils and rare dysplastic forms. The blood film features were consistent with severe B12 deficiency. However, the presence of significant red cell fragmentation and raised LDH levels raised the possibility of pseudothrombotoic microangiopathy.

Figure 1: Typical blood film features of severe B12 deficiency.

A diagnosis of nutritional B12 deficiency was made. Further history from the patient’s mother, who was of Indian ethnicity, revealed that she had been adhering to a strict vegan diet since childhood, devoid of all animal-based products owing to cultural reasons. Mother was tested and noted to be severely B12 deficient as well. Although known to be vegan, no B12 supplementation was given during antenatal care.

Our patient was treated with daily subcutaneous B12 injections. Evidence of marrow recovery was seen with reticulocytosis day 4 post-treatment. Follow-up blood counts were stable and neurological improvement was. noticed prior to discharge, with improved general tone and less irritability.

On follow-up at one month she was noted to have achieved new gross and fine motor milestones. She was more alert, less irritable, able to pull to sit with support, was tracking objects in front of her and was bringing her arms up to reach for objects. The patient was discharged with ongoing B12 supplementation to be guided by a dietician. The family subsequently moved out of town and was referred to their local paediatric service for ongoing developmental follow-up.

Discussion

We have reported symptomatic anaemia and thrombocytopenia as a severe manifestation of infantile B12 deficiency. Our patient presented late, with the full spectrum of haematological and neurological manifestations.

Thrombocytopenia, although less common, has also been attributed to B12 deficiency. Severe B12 deficiency has been reported to trigger pseudo-thrombotic microangiopathy(pseudo-TMA) causing haemolytic anaemia and thrombocytopenia.1 This well-described clinicopathological entity, which represents 2.5% of haematological disorders associated with B12 deficiency, presents similar to haemolytic uraemic syndrome (HUS), occasionally with its accompanying renal manifestations.2

Serum B12 levels are a poorly sensitive marker of early deficiency and clinical manifestations of this can be subtle in infants. Hence, we believe that infantile B12 deficiency is more widespread and under-recognised. Serum methylmalonic acid (MMA) and homocysteine levels have been used as a sensitive functional marker of early B12 deficiency.3,4 However, these measurements are not routinely tested for or available in many community labs in New Zealand.

In most cases, infantile B12 deficiency is a consequence of maternal deficiency.5 Healthy newborns acquire B12 stores trans-placentally that typically last the first few weeks of life. Hence, exclusively breastfed newborns are dependent upon the B12 content of breastmilk. The B12 content of breastmilk is largely dependent on the mother’s current B12 intake rather than stores.6 As a consequence, exclusive breastfed infants of B12 deficient mothers, who are not supplemented, present in the first few months of life with severe deficiency.

Although the precise incidence of B12 deficiency in infants is unknown, an American newborn screening program reported a rate of 0.88/100,000 births [95% (CI) 0.60–1.26).7 With the increased uptake of vegan lifestyles in the last decade among women and increased emphasis on exclusive breastfeeding in the developed world, we expect infantile B12 deficiency to be on the rise. Current guidelines by RANZCOG recommend B12 supplementation in pregnancy and lactation for vegan mothers. Unfortunately, we do not have data on rates of compliance to this guidance across the varied settings of antenatal care in hospitals and communities in New Zealand. We have highlighted this case to bring awareness to infantile B12 deficiency as a preventable public health issue.

In summary, we would like to highlight infantile B12 deficiency and its potentially severe manifestations if left untreated. Infantile B12 deficiency is an important preventable public health problem that can be difficult to detect but can be managed with appropriate antenatal screening and supplementation of at-risk pregnant women.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Vivek Rajasekaran, Paediatric Registrar, Waikato District Health Board, Hamilton; Joanna Sheriff, Paediatrician, Waikato District Health Board, Hamilton; Helen Moore, Haematologist, Waikato District Health Board, Hamilton; Hamish McCay, Paediatrician, Waikato District Health Board, Hamilton; Mark Winstanley, Paediatrician, Starship Hospital, Auckland.

Acknowledgements

Correspondence

Dr Vivek Rajasekaran, Elizabeth Rothwell Building, Level 6, Waikato Hospital, Pembroke and Selwyn Street, Hamilton 3240.

Correspondence Email

vivek.rajasekaran@waikatodhb.health.nz

Competing Interests

Nil.

1. Fahmawi Y, Campos Y, Khushman M, Alkharabsheh O, Manne A, Zubair H, et al. Vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy: a case report and literature review. Clin Pharmacol. 2019; 11:127–31.

2. Mullikin D, Pillai N, Sanchez R, O'Donnell-Luria AH, Kritzer A, Tal L, et al. Megaloblastic Anemia Progressing to Severe Thrombotic Microangiopathy in Patients with Disordered Vitamin . J Pediatr. 2018 11; 202:315-319.e2.

3. Roach ES, McLean WT. Neurologic disorders of vitamin b12 deficiency. American family physician. 1982 Jan; 25(1):111–5.

4. Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008 Oct; 105(40):680–5.

5. Roumeliotis N, Dix D, Lipson A. Vitamin B(12) deficiency in infants secondary to maternal causes. CMAJ. 2012; 184(14):1593–1598. doi:10.1503/cmaj.112170

6. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.

7. Hinton CF, Ojodu JA, Fernhoff PM, Rasmussen SA, Scanlon KS, Hannon WH. Maternal and neonatal vitamin B12 deficiency detected through expanded newborn screening—United States, 2003–2007. The Journal of Pediatrics. 2010 Jul 1; 157(1):162–3.

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Although vitamin B12 deficiency is a well-established cause of severe anaemia with macrocytosis in infants, severe thrombocytopenia has been less commonly reported. In this report, we describe an uncommon case of an infant with severe vitamin B12 deficiency presenting with severe anemia and thrombocytopenia, and discuss its implications as a potentially preventable public health problem.

Case report

An exclusively breastfed eight-month-old girl, who had been unsuccessful with attempts to wean on to solids, presented to the emergency room unwell with fever. She was diagnosed with a right lower lobe pneumonia. Incidentally, she was remarkably pale with mucosal bleeding and fine petechiae on her trunk and limbs. Further history revealed black tarry stools typical of melaena.

On examination, the infant was found to be generally irritable with central hypotonia and significant gross, fine motor delay. At rest, the infant was floppy with frog-leg posturing. She was unable to pull to sit and showed marked head lag, poor head control. She was also unable to track objects of interest or bring her arms to midline and reach for objects. She was also found not to mimic facial expressions or have a social smile.

Laboratory investigations show a severe macrocytic anaemia, thrombocytopenia along with profoundly low B12 levels (Table 1). Although folate and iron studies were within normal range, she was also found to have vitamin D deficiency with hypocalcemia.

Table 1: Laboratory investigations.

The blood film showed marked red cell anisopoikilocytosis with tear drop poikilocytes, stippled cells, macrocytes, many fragmented cells and occasional dysplastic nucleated red cells (Figure 1). Platelet count was low but morphologically normal. White blood cells showed occasional hypersegmented neutrophils and rare dysplastic forms. The blood film features were consistent with severe B12 deficiency. However, the presence of significant red cell fragmentation and raised LDH levels raised the possibility of pseudothrombotoic microangiopathy.

Figure 1: Typical blood film features of severe B12 deficiency.

A diagnosis of nutritional B12 deficiency was made. Further history from the patient’s mother, who was of Indian ethnicity, revealed that she had been adhering to a strict vegan diet since childhood, devoid of all animal-based products owing to cultural reasons. Mother was tested and noted to be severely B12 deficient as well. Although known to be vegan, no B12 supplementation was given during antenatal care.

Our patient was treated with daily subcutaneous B12 injections. Evidence of marrow recovery was seen with reticulocytosis day 4 post-treatment. Follow-up blood counts were stable and neurological improvement was. noticed prior to discharge, with improved general tone and less irritability.

On follow-up at one month she was noted to have achieved new gross and fine motor milestones. She was more alert, less irritable, able to pull to sit with support, was tracking objects in front of her and was bringing her arms up to reach for objects. The patient was discharged with ongoing B12 supplementation to be guided by a dietician. The family subsequently moved out of town and was referred to their local paediatric service for ongoing developmental follow-up.

Discussion

We have reported symptomatic anaemia and thrombocytopenia as a severe manifestation of infantile B12 deficiency. Our patient presented late, with the full spectrum of haematological and neurological manifestations.

Thrombocytopenia, although less common, has also been attributed to B12 deficiency. Severe B12 deficiency has been reported to trigger pseudo-thrombotic microangiopathy(pseudo-TMA) causing haemolytic anaemia and thrombocytopenia.1 This well-described clinicopathological entity, which represents 2.5% of haematological disorders associated with B12 deficiency, presents similar to haemolytic uraemic syndrome (HUS), occasionally with its accompanying renal manifestations.2

Serum B12 levels are a poorly sensitive marker of early deficiency and clinical manifestations of this can be subtle in infants. Hence, we believe that infantile B12 deficiency is more widespread and under-recognised. Serum methylmalonic acid (MMA) and homocysteine levels have been used as a sensitive functional marker of early B12 deficiency.3,4 However, these measurements are not routinely tested for or available in many community labs in New Zealand.

In most cases, infantile B12 deficiency is a consequence of maternal deficiency.5 Healthy newborns acquire B12 stores trans-placentally that typically last the first few weeks of life. Hence, exclusively breastfed newborns are dependent upon the B12 content of breastmilk. The B12 content of breastmilk is largely dependent on the mother’s current B12 intake rather than stores.6 As a consequence, exclusive breastfed infants of B12 deficient mothers, who are not supplemented, present in the first few months of life with severe deficiency.

Although the precise incidence of B12 deficiency in infants is unknown, an American newborn screening program reported a rate of 0.88/100,000 births [95% (CI) 0.60–1.26).7 With the increased uptake of vegan lifestyles in the last decade among women and increased emphasis on exclusive breastfeeding in the developed world, we expect infantile B12 deficiency to be on the rise. Current guidelines by RANZCOG recommend B12 supplementation in pregnancy and lactation for vegan mothers. Unfortunately, we do not have data on rates of compliance to this guidance across the varied settings of antenatal care in hospitals and communities in New Zealand. We have highlighted this case to bring awareness to infantile B12 deficiency as a preventable public health issue.

In summary, we would like to highlight infantile B12 deficiency and its potentially severe manifestations if left untreated. Infantile B12 deficiency is an important preventable public health problem that can be difficult to detect but can be managed with appropriate antenatal screening and supplementation of at-risk pregnant women.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Vivek Rajasekaran, Paediatric Registrar, Waikato District Health Board, Hamilton; Joanna Sheriff, Paediatrician, Waikato District Health Board, Hamilton; Helen Moore, Haematologist, Waikato District Health Board, Hamilton; Hamish McCay, Paediatrician, Waikato District Health Board, Hamilton; Mark Winstanley, Paediatrician, Starship Hospital, Auckland.

Acknowledgements

Correspondence

Dr Vivek Rajasekaran, Elizabeth Rothwell Building, Level 6, Waikato Hospital, Pembroke and Selwyn Street, Hamilton 3240.

Correspondence Email

vivek.rajasekaran@waikatodhb.health.nz

Competing Interests

Nil.

1. Fahmawi Y, Campos Y, Khushman M, Alkharabsheh O, Manne A, Zubair H, et al. Vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy: a case report and literature review. Clin Pharmacol. 2019; 11:127–31.

2. Mullikin D, Pillai N, Sanchez R, O'Donnell-Luria AH, Kritzer A, Tal L, et al. Megaloblastic Anemia Progressing to Severe Thrombotic Microangiopathy in Patients with Disordered Vitamin . J Pediatr. 2018 11; 202:315-319.e2.

3. Roach ES, McLean WT. Neurologic disorders of vitamin b12 deficiency. American family physician. 1982 Jan; 25(1):111–5.

4. Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008 Oct; 105(40):680–5.

5. Roumeliotis N, Dix D, Lipson A. Vitamin B(12) deficiency in infants secondary to maternal causes. CMAJ. 2012; 184(14):1593–1598. doi:10.1503/cmaj.112170

6. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.

7. Hinton CF, Ojodu JA, Fernhoff PM, Rasmussen SA, Scanlon KS, Hannon WH. Maternal and neonatal vitamin B12 deficiency detected through expanded newborn screening—United States, 2003–2007. The Journal of Pediatrics. 2010 Jul 1; 157(1):162–3.

For the PDF of this article,
contact nzmj@nzma.org.nz

View Article PDF

Although vitamin B12 deficiency is a well-established cause of severe anaemia with macrocytosis in infants, severe thrombocytopenia has been less commonly reported. In this report, we describe an uncommon case of an infant with severe vitamin B12 deficiency presenting with severe anemia and thrombocytopenia, and discuss its implications as a potentially preventable public health problem.

Case report

An exclusively breastfed eight-month-old girl, who had been unsuccessful with attempts to wean on to solids, presented to the emergency room unwell with fever. She was diagnosed with a right lower lobe pneumonia. Incidentally, she was remarkably pale with mucosal bleeding and fine petechiae on her trunk and limbs. Further history revealed black tarry stools typical of melaena.

On examination, the infant was found to be generally irritable with central hypotonia and significant gross, fine motor delay. At rest, the infant was floppy with frog-leg posturing. She was unable to pull to sit and showed marked head lag, poor head control. She was also unable to track objects of interest or bring her arms to midline and reach for objects. She was also found not to mimic facial expressions or have a social smile.

Laboratory investigations show a severe macrocytic anaemia, thrombocytopenia along with profoundly low B12 levels (Table 1). Although folate and iron studies were within normal range, she was also found to have vitamin D deficiency with hypocalcemia.

Table 1: Laboratory investigations.

The blood film showed marked red cell anisopoikilocytosis with tear drop poikilocytes, stippled cells, macrocytes, many fragmented cells and occasional dysplastic nucleated red cells (Figure 1). Platelet count was low but morphologically normal. White blood cells showed occasional hypersegmented neutrophils and rare dysplastic forms. The blood film features were consistent with severe B12 deficiency. However, the presence of significant red cell fragmentation and raised LDH levels raised the possibility of pseudothrombotoic microangiopathy.

Figure 1: Typical blood film features of severe B12 deficiency.

A diagnosis of nutritional B12 deficiency was made. Further history from the patient’s mother, who was of Indian ethnicity, revealed that she had been adhering to a strict vegan diet since childhood, devoid of all animal-based products owing to cultural reasons. Mother was tested and noted to be severely B12 deficient as well. Although known to be vegan, no B12 supplementation was given during antenatal care.

Our patient was treated with daily subcutaneous B12 injections. Evidence of marrow recovery was seen with reticulocytosis day 4 post-treatment. Follow-up blood counts were stable and neurological improvement was. noticed prior to discharge, with improved general tone and less irritability.

On follow-up at one month she was noted to have achieved new gross and fine motor milestones. She was more alert, less irritable, able to pull to sit with support, was tracking objects in front of her and was bringing her arms up to reach for objects. The patient was discharged with ongoing B12 supplementation to be guided by a dietician. The family subsequently moved out of town and was referred to their local paediatric service for ongoing developmental follow-up.

Discussion

We have reported symptomatic anaemia and thrombocytopenia as a severe manifestation of infantile B12 deficiency. Our patient presented late, with the full spectrum of haematological and neurological manifestations.

Thrombocytopenia, although less common, has also been attributed to B12 deficiency. Severe B12 deficiency has been reported to trigger pseudo-thrombotic microangiopathy(pseudo-TMA) causing haemolytic anaemia and thrombocytopenia.1 This well-described clinicopathological entity, which represents 2.5% of haematological disorders associated with B12 deficiency, presents similar to haemolytic uraemic syndrome (HUS), occasionally with its accompanying renal manifestations.2

Serum B12 levels are a poorly sensitive marker of early deficiency and clinical manifestations of this can be subtle in infants. Hence, we believe that infantile B12 deficiency is more widespread and under-recognised. Serum methylmalonic acid (MMA) and homocysteine levels have been used as a sensitive functional marker of early B12 deficiency.3,4 However, these measurements are not routinely tested for or available in many community labs in New Zealand.

In most cases, infantile B12 deficiency is a consequence of maternal deficiency.5 Healthy newborns acquire B12 stores trans-placentally that typically last the first few weeks of life. Hence, exclusively breastfed newborns are dependent upon the B12 content of breastmilk. The B12 content of breastmilk is largely dependent on the mother’s current B12 intake rather than stores.6 As a consequence, exclusive breastfed infants of B12 deficient mothers, who are not supplemented, present in the first few months of life with severe deficiency.

Although the precise incidence of B12 deficiency in infants is unknown, an American newborn screening program reported a rate of 0.88/100,000 births [95% (CI) 0.60–1.26).7 With the increased uptake of vegan lifestyles in the last decade among women and increased emphasis on exclusive breastfeeding in the developed world, we expect infantile B12 deficiency to be on the rise. Current guidelines by RANZCOG recommend B12 supplementation in pregnancy and lactation for vegan mothers. Unfortunately, we do not have data on rates of compliance to this guidance across the varied settings of antenatal care in hospitals and communities in New Zealand. We have highlighted this case to bring awareness to infantile B12 deficiency as a preventable public health issue.

In summary, we would like to highlight infantile B12 deficiency and its potentially severe manifestations if left untreated. Infantile B12 deficiency is an important preventable public health problem that can be difficult to detect but can be managed with appropriate antenatal screening and supplementation of at-risk pregnant women.

Summary

Abstract

Aim

Method

Results

Conclusion

Author Information

Vivek Rajasekaran, Paediatric Registrar, Waikato District Health Board, Hamilton; Joanna Sheriff, Paediatrician, Waikato District Health Board, Hamilton; Helen Moore, Haematologist, Waikato District Health Board, Hamilton; Hamish McCay, Paediatrician, Waikato District Health Board, Hamilton; Mark Winstanley, Paediatrician, Starship Hospital, Auckland.

Acknowledgements

Correspondence

Dr Vivek Rajasekaran, Elizabeth Rothwell Building, Level 6, Waikato Hospital, Pembroke and Selwyn Street, Hamilton 3240.

Correspondence Email

vivek.rajasekaran@waikatodhb.health.nz

Competing Interests

Nil.

1. Fahmawi Y, Campos Y, Khushman M, Alkharabsheh O, Manne A, Zubair H, et al. Vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy: a case report and literature review. Clin Pharmacol. 2019; 11:127–31.

2. Mullikin D, Pillai N, Sanchez R, O'Donnell-Luria AH, Kritzer A, Tal L, et al. Megaloblastic Anemia Progressing to Severe Thrombotic Microangiopathy in Patients with Disordered Vitamin . J Pediatr. 2018 11; 202:315-319.e2.

3. Roach ES, McLean WT. Neurologic disorders of vitamin b12 deficiency. American family physician. 1982 Jan; 25(1):111–5.

4. Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008 Oct; 105(40):680–5.

5. Roumeliotis N, Dix D, Lipson A. Vitamin B(12) deficiency in infants secondary to maternal causes. CMAJ. 2012; 184(14):1593–1598. doi:10.1503/cmaj.112170

6. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.

7. Hinton CF, Ojodu JA, Fernhoff PM, Rasmussen SA, Scanlon KS, Hannon WH. Maternal and neonatal vitamin B12 deficiency detected through expanded newborn screening—United States, 2003–2007. The Journal of Pediatrics. 2010 Jul 1; 157(1):162–3.

Contact diana@nzma.org.nz
for the PDF of this article

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